Terminal Nerve GnRH3 Neurons Mediate Slow Avoidance of Carbon Dioxide in Larval Zebrafish

Abstract

Summary: Escape responses to threatening stimuli are vital for survival in all animal species. Larval zebrafish display fast escape responses when exposed to tactile, acoustic, and visual stimuli. However, their behavioral responses to chemosensory stimuli remain unknown. In this study, we found that carbon dioxide (CO2) induced a slow avoidance response, which was distinct from the touch-evoked fast escape response. We identified the gonadotropin-releasing hormone 3-expressing terminal nerve as the CO2 sensor in the nose. Wide-field calcium imaging revealed downstream CO2-activated ensembles of neurons along three distinct neural pathways, olfactory, trigeminal, and habenulo-interpeduncular, further reaching the reticulospinal neurons in the hindbrain. Ablation of the nose, terminal nerve, or trigeminal ganglion resulted in a dramatic decrease in CO2-evoked avoidance responses. These findings demonstrate that the terminal nerve-trigeminal system plays a pivotal role in triggering a slow chemosensory avoidance behavior in the larval zebrafish. : CO2 avoidance is a fundamental behavior conserved across diverse animal phyla for survival. Koide et al. show that CO2 elicits a distinct, slow avoidance response in larval zebrafish. Calcium imaging and surgical or laser ablation experiments reveal a crucial role for the terminal nerve or trigeminal system in mediating the CO2-evoked avoidance response. Keywords: zebrafish, escape behavior, avoidance behavior, chemosensory system, terminal nerve, GnRH, carbon dioxide, neural activity imaging, nasal trigeminal pathway